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e19535 Background: Renal impairment has been negatively associated with progression free survival and overall survival in patients diagnosed with multiple myeloma (MM). Autologous stem cell transplant (ASCT) has become a standard of care for treatment in MM. Most previous studies have assessed the safety of ASCT and the improvement in renal function in patients with MM. However, a critical question about renal function over time, and its impact on survival after ASCT has rarely been addressed. In our study we sought to understand how renal function was impacted over time, the predictors of renal function, and overall survival after ASCT. Methods: We performed a retrospective review of all MM patients who underwent ASCT at MDACC from January1, 2008 through December 31, 2013. A total of 885 none dialysis patients who received Melphalan alone as the conditioning regimen were identified. We collected demographic information, ISS stage, and disease status at time of transplant and at last follow up. Creatinine, GFR (calculated using CKD Epi equation), calcium, and LDH were also collected at day 0, 100, 180, & 365. Given the longitudinal nature of the data, linear mixed effect models were used to study the change of GFR over time. A joint model approach for longitudinal and survival data was used to assess association between overall survival and GFR with patient’s age at transplant, ISS, disease status, disease risk category and response to treatment prior to transplant included in the linear mixed effect models and hazard models. As sensitivity analyses, landmark analyses were conducted with day 0, 100, 180, and 365 days post-transplant as landmark time points. Results: Patients’ GFR at post-transplant time points were significantly higher (p ≤ 0.025) compared to the day of ASCT. A higher ISS stage at diagnosis was significantly associated with a lower GFR (p < .0001) at all stages of chronic kidney disease. Specifically, compared to the patients with ISS stage I, those with ISS stage II or higher had lower GFR across all time points (p ≤ .0003). GFR value was not significantly associated with OS in any of the analyses described above. In contrast, disease status, ISS stage, response to induction prior to SCT were all associated with shorter OS. Conclusions: The study demonstrates in a large cohort and in a longitudinal manner that MM patients who underwent ASCT did not have further decline in GFR over time. In addition, GFR was strongly associated with ISS stage. As far as OS, MM-related factors significantly impacted the survival while GFR did not.

74 Background: NK cells have potent antitumor and antiviral effects. We hypothesized that multiple infusions of high doses of mb-IL21 ex vivo expanded NK cells administered peri-transplant will enhance graft-versus-leukemia effect and decrease viral reactivation. Methods: In the phase 1 dose escalation study patients received NK cells starting at 1x105 to 1x108/Kg/dose (N = 13). No dose limiting toxicities were observed. In the phase 2 study, 12 patients with myeloid malignancies received mbIL-21 ex vivo expanded NK cells at dose 1x108NK cells/kg with a K562 feeder cell system and with 41BB. NK cells were generated from peripheral blood mononuclear cells of the same donor and infused fresh on day -2, and cryopreserved on day +7 and +28. Conditioning regimen consisted of melphalan, fludarabine and TBI. All patients had bone marrow graft. Here we report updated results of all patients treated to date on this study. Results: Twenty-five patients (18 AML/MDS and 7 CML) were treated to date. The median age was 45 years, the median follow-up of survivors was 28 months. 16/18 AML/MDS patients had high-risk disease. No adverse effects occurred. Engraftment was achieved in all 24 evaluable patients after a median of 19 days. The cumulative incidence (CI) of grade 2 aGVHD was 38% at day 100. No chronic GVHD was observed. The CI of TRM was 21% at 2 years. The CI of relapse at 1 year was 8%. The 2-years PFS was 66%. Ten patients reactivated CMV. Immunologic reconstitution of T cell subsets showed a 5.7 fold higher number of NK cells on day 28 in patients who received highest NK cell doses vs. others. A matched-pair analysis done with an independent CIBMTR cohort of patients who received either MAC (N = 61) or RIC (N = 57), showed a significantly improvement in relapse rate and PFS in favor of patients treated on trial. Conclusions: Administration of higher doses of NK cells was associated with higher NK cell numbers early post-transplant, suggesting that a dose-dependent effect could be achieved. A low relapse rate and lower viral reactivation post-transplant continues to be seen, suggesting that NK cells exert both anti-tumor and antiviral effects in this setting. Clinical trial information: NCT01904136.

Purpose We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin’s lymphoma (NHL). Patients and Methods Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m2 and 7 days after chemotherapy at 1,000 mg/m2), together with granulocyte colony-stimulating factor 10 μg/kg and granulocyte-macrophage colony-stimulating factor 250 μg/m2 administered subcutaneously daily. HD-R of 1,000 mg/m2 was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab. Results With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to ≥ 500 cells/μL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab. Conclusion The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Purpose Allogeneic transplantation for patients with lymphoma who experience a recurrence after an autologous transplantation has been considered a hazardous therapeutic choice. We investigated the safety and efficacy of nonmyeloablative stem-cell transplantation in these patients. Patients and Methods Patients were required to have chemosensitive or stable disease. Twenty consecutive patients were treated in two sequential trials. Fifteen patients underwent a preparative regimen of fludarabine (30 mg/m2 daily for 3 days), intravenous cyclophosphamide (750 mg/m2 daily for 3 days), and rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 continuous infusion daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. Results All patients experienced engraftment of donor cells. One patient (5%) experienced grade 2 acute graft-versus-host disease, and no patients experienced a higher grade. One patient experienced disease progression at 115 days post-transplantation and responded to donor lymphocyte infusion. The remaining patients remained disease-free. One patient died at 10.5 months from a fungal infection. With a median follow-up time of 25 months, the estimated 3-year current progression-free survival rate was 95%. Conclusion These data suggest that nonmyeloablative allogeneic stem-cell transplantation is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.

Purpose: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. Patients and Methods: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. Results: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). Conclusion:Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.

7046 Background: We previously reported 6% 100 day NRM with a MA fludarabine (Flu) and busulfan (Bu) in older patients with a median age of 60 years. MA dose of Bu in this timed sequential (TS) regimen was administered over a longer period of time. To assess its impact on survival, we compared the outcomes of older patients treated with the TS Bu (TS cohort) or the RIC Flu/Bu regimen, which is used as standard (ST) for older patients at our center (ST cohort). Methods: Patients in the TS cohort received IV Bu 80 mg/m2/d on day -13 and -12 and Flu 40 mg/m2/d followed by IV Bu on day -6 to -3, dose adjusted to achieve a total Bu course AUC of 20,000 μmol-min based on PK studies. Patients in the ST cohort received Flu 40 mg/m2day followed by IV Bu daily for 4 days (day -6 to -3) dosed to achieve AUC of 16,000 μmol-min. Patients with AML or MDS were eligible for the study if they had adequate organ function, had matched related or unrelated donor and were treated between Jan 2012 and Sept 2016. Results: 162 patients, 50 with MDS and 112 with AML, were included in this study. Patient characteristics including age, sex, disease status, cytogenetic risk group, donor type, graft source CMV status and comorbidity were well balanced and without any significant difference in the two cohorts. Median age was 66 and 65 years in ST and TS cohorts, respectively. Overall survival (OS) and progression free survival (PFS) were significantly better in the TS cohort (see Table). This was due to a reduction in the disease progression without any increase in the non-relapse mortality (NRM). After adjusting for other covariates, the multivariate analysis for PFS confirmed longer PFS with TS Bu regimen (HR: 0.36; P=0.003). The benefit was mainly seen in patients with a comorbidity score ≤ 3. Conclusions: The myeloablative timed sequential Bu regimen improves survival and appears promising in older patients with AML/MDS. Clinical trial information: NCT01572662. [Table: see text]

8561 Background: The role of alloHCT and conditioning intensity in DLBCL remains unclear. In this retrospective study, we determined their effectiveness in 116 patients (pts) with DLBCL (de novo, n=59, transformed, n=57) receiving alloHCT at our institution, between 1998-2011. Methods: Median age was 51years (range, 19-70); median prior therapies was 4 (range 2-12). Disease status at alloHCT was complete response (CR) (n=22), partial response (PR) (n=58), stable (SD) (n=25) or progressive disease (PD) (n=11). 41 (35%) pts had previous autografts. 74 (64%) pts received RIC of melphalan/fludarabine (Flu) or BEAM, and 42 (36%) received a NMA conditioning of Flu/cyclophosphamide or cisplatin/cytarabine/ Flu. Donor source was HLA-identical sibling (MRD) (65%), HLA-matched unrelated (MUD) (31%) or a 1-Ag mismatched donor (4%). Results: With median follow-up among survivors of 63 months (range 5-157), estimated 5-yr OS and PFS for the whole cohort was 41% and 34% respectively. On multivariate (MV) analysis, disease status was most significant predictor for OS, with chemo refractory disease (SD/PD) being associated with higher mortality rate (HR 3.7, 95% CI 1.6-8.6, p=0.002). Combined use of NMA conditioning and MRD was associated with significantly lower mortality rate (HR 0.4, 95% CI 1.6-8.6, p=0.005). OS was highest [69% (95% CI 49-82)} for pts in CR/PR after NMA with a MRD (n=29), and lowest [(12% (95% CI 3-29)] for SD/PD pts after RIC with a non MRD (n=32). Disease status was strongest predictor of PFS on MV analysis, with CR pts having improved PFS compared to SD/PD (5-year estimates of 58% and 13%, respectively (P

e18511 Background: We previously reported the use of fludarabine, rituximab and cyclophosphamide as a nonmyeloablative conditioning for lymphomas (Khouri et al, Blood 2008;111:5530). Bendamustine i...

6565 Background: Despite the advent of novel agents, outcomes of TCL with conventional chemotherapy are poor. We have previously reported encouraging results with ASCT (Rodriguez J, J Clin Oncol, 2001). Herein, we report our long-term experience in 126 patients (pts). Methods: This is a retrospective analysis of TCL pts treated at our institution between 1986 and 2009. Median age was 49 years and 65% were males. Histologies included 1)peripheral t-cell lymphoma not otherwise specified (PTCL -NOS=42, 2) anaplastic large cell lymphoma (ALCL=47) of which 9 pts were ALK(+), 3) angioimmunoblastic (AILT=15), 4) NK cell lymphomas (N=6), Hepatosplenic TCL (HS-TCL=6), others (n=10). Results: At transplant, 33% were in first remission (CR1), 51% had chemosensitive relapse, 16 % had refractory disease. Most pts received BEAM or BEAM like (82%) conditioning. With a median follow-up of 39 months, overall survival (OS) and progression-free-survival (PFS) estimates were 39% (95% CI, 28-50), and 30%(95% CI 20-41). Treatm...

e19507 Background: Age at diagnosis is a poor prognostic factor for overall survival after standard therapy for HD. Whether older age is a prognostic factor for outcome after autologous transplantation is not known. We sought to evaluate the effect of older age at diagnosis on transplant outcome. Patients and Methods: All patients with HD undergoing autologous transplantation with BEAM conditioning (BCNU, Etoposide, Cytarabine, and Melphalan) between January 1996 and December 2007 were included in this study. During these 12 years, 248 patients (103 males) underwent autologous transplantation. Seventy two patients (29%) were older than 40 years of age at the time of initial diagnosis. Median age at transplantation was 31 years (range 11–74). At transplantation, 63 (25%) were in complete remission (CR); 148 (60%) were in partial remission (PR); and 37 (15%) had stable (SD) or progressive disease (PD). Forty-six patients (19%) had received more than 3 courses of chemotherapy prior to transplantation. LDH was elevated in 131 (53%). Peripheral blood stem cells were used as stem cell source in 241 (97%) patients. Results: With a median follow up of 48 months (range, 1–143 months), the 48-month overall (OS) and event-free survival (EFS) were 72% (95% CI; 65%-77%) and 57% (95% CI; 50%-63%), respectively. The cumulative incidence of non-relapse mortality at 1 year was 1.6%. The cumulative incidence of secondary MDS or AML was 8%. In univariate analysis, disease status (p [Table: see text] No significant financial relationships to disclose.

7040 Background: Patients (pts) with relapsed/refractory non-Hodgkin's lymphoma (NHL) who fail to mobilize adequate peripheral blood stem cells (PBSC) often undergo bone marrow (BM) harvest for autologous transplantation. The outcome of these pts is not known. Methods: In this retrospective study (May 1996-September 2006), we identified 36 out of a total of 750 pts with advanced NHL, who failed to collect adequate PBSC and subsequently underwent BM harvest followed by ABMT. Decision to harvest BM was left to the treating clinician. Median age at transplant was 53 years (range 15–73). Twenty of 36 pts (55%) were male. Histology was intermediate grade in 31 (86%) patients and low grade in 5 (14%). Twelve pts (35%) had history of BM involvement with lymphoma. Median number of chemotherapy cycles received prior to mobilization was 3 (range 1–6). At the time of stem cell mobilization 18 (50%) were in complete remission (CR), 13 (37%) were in partial remission (PR) and 5 (13%) had progressive disease (PD). Twenty four (67%) pts underwent chemo-mobilization and 12 (33%) were mobilized with cytokines alone. Results: The median total nucleated cell dose and CD34+ cell dose harvested/kg were 3.72 x 108 (range 0.25–58.0) and 1.6 x 106 (range 0.03–5.8), respectively. After ABMT, 33 of 35 evaluable (94%) pts engrafted neutrophils with median time to ANC 0.5 x 109/L of 23 days (range 8–47). Median time to platelet count 20 x 109/L was 63 days (range 11–375). Two of 35 (6 %) evaluable pts failed to engraft. After ABMT, 25/36 (70%) pts achieved a CR. The incidence of NRM at 100 days was 15%. Sixteen (45%) pts relapsed at a median of 11 months (range 2–59) from ABMT. After a median follow-up of 34 months (range 0.4–100), the 3-year OS and DFS were 47% and 35%, respectively. Causes of death were: disease progression/relapse in 15 (60%), secondary malignancy in 3 (12%), multiorgan failure in 5 (20%), and unknown in 2 (8%). Conclusions: ABMT is feasible in pts who fail to mobilize adequate PBSC, however, these pts have longer time to engraftment. Although the CR rate after transplant is high, the NRM is higher than expected. Non-myeloablative allogeneic transplantation may provide better outcomes with similar toxicity and needs to be further studied. No significant financial relationships to disclose.

7099 Background: High-dose therapy and allogeneic stem cell transplantation (allo SCT) is a potentially curative treatment for patients with hematologic malignancies. Due to a high risk of regimen-related toxicity, only patients with excellent organ-system function are considered eligible for this treatment. A low left ventricular ejection fraction (LVEF) of ≤ 45% is considered to be a major risk factor for post-transplant cardiac toxicity and nonrelapse mortality. However, several patients with advanced hematologic malignancies and low LVEF can potentially benefit from this therapy. To address this issue, we studied the incidence of cardiac toxicity and non-relapse mortality (NRM) in 56 patients with low LVEF undergoing allo SCT. Methods: We performed a retrospective analysis on 56 patients with impaired cardiac function, who underwent an allo SCT between January 2000 and February 2006 at our institution. Pre-transplant evaluation included bidimensional echocardiogram and an electrocardiogram. Cardiac toxicity was defined as congestive heart failure (CHF), atrial / ventricular arrhythmia or acute myocardial ischemia. Twenty-two patients received a myeloablative (16 busulfan-based, 6 TBI-based), while 34 patients received a fludarabine-based reduced-intensity preparative regimen. Results: Twenty-three patients (41%) received allo SCT from an unrelated donor. Acute leukemia was the reason for allo SCT in 32 (57%) patients. Baseline LVEF, within 30 days prior to allo SCT, ranged from 20 to 45%. After a minimum of 6-month follow up, cardiac toxicity was seen in 7 (12%) patients. That included CHF in 4 (7%) and atrial fibrillation (AF) in 4 (7%). One patient had both CHF and AF. There were no documented episodes of acute myocardial ischemia. Cumulative incidence of NRM at 100 days was 12%, none of the deaths being attributable to a cardiac cause. These were comparable to allo SCT performed in patients with normal LVEF. Age, degree of left vetricular dysfunction, type of transplant or the underlying disease did not emerge as significant predictors of post-transplant cardiac toxicity or NRM. Conclusions: Allogeneic SCT is feasible in patients with hematologic malignancies and low LVEF. A prospective study with stratification for cardiac risk factors is warranted in patients with low LVEF. No significant financial relationships to disclose.

6518 Background: P/G status has been suggested to be an important predictor of outcome in pts with LBCL who receive an ASCT. Newer conditioning regimens which include HDR have been shown to improve results (Khouri, JCO, 2005). The influence of HDR on the outcome of pts based on P/G status has not been determined. Methods: A retrospective review of pts with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Results: A total of 188 pts were identified. Median age was 49 yrs with 108 (57%) male pts. 147 (78%) had de novo LBCL and 41 (22%) had an LBCL of follicular origin (LBCL-F). 83 (39%) pts received HDR with ASCT. At transplantation 95 pts (50%) were in PR, 71 pts (38%) in CRU and 22 pts (12%) in CR. 142 (76%) pts were P/G negative, 37 (20%) pts P/G positive and 9 (4%) pts unknown. The median follow-up was 44 months. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and P/G status. On multivariate analysis, P/G status and HDR were the only predictors for progression and PFS. Pts who were P/G negative and those that received HDR had a hazard ratio (HR) of 0.3 (p [Table: see text] No significant financial relationships to disclose.

6559 Background and Purpose: In aggressive CLL, the presence of an unmutated IgVH gene is strongly associated with the expression of ZAP-70. We used immunohistochemical techniques and routinely fix...

6657 Introduction: Chronic graft versus host disease (cGVHD) remains a major complication in hematopoietic transplant recipients. We conducted a phase II trial of sirolimus in combination with tacr...